The objective of this proposal is to develop a better understanding of organ, cell and subcellular injury produced by shock and hypoxia which are commonly encountered by surgeons. The major thrust of the proposal will be a detailed and systematic study of alterations in cell function produced by low blood flow and deficient oxygenation. Beginning at this basic level the work will proceed then to organ systems and the intact organism in attempts to correlate this with gross hemodynamic and metabolic events, to correct alteration in function and improve treatment in man. The long range goal is to improve our understanding and treatment of the injured or sick patient. Work will be divided into several component areas which are closely inter-related: 1. Alterations in cell and subcellular function with shock and hypoxia: a. Mitochondrial metabolism in shock; b. Active transport in shock; c. Energy contents of cells in shock; d. Effects of steroids in shock. 2. Relationships of the lung and circulatory failure: a. Is there such a thing as the "shock lung?" b. Septic shock and ventilation; c. Effect of pulsatile bypass on the lungs. 3. General studies of shock and related subjects: a. Continuation of isoproterenol studies and other vasoactive agents; b. Interstitial fluid pressure; c. Hypocalcemia and pancreatitis.